Expression and function of alternative splice variants of the mouse TGF-beta type I receptor

Mouse TGF-beta type I receptor, Alk5, encodes two types of mRNA generated by alternative splicing of four amino acids in the extracellular region. In the present study, the expression and function of alternative splice variants of Alk5, i.e., Alk5-L (Alk5 with the four amino acids) and Alk5-S (Alk5 without the four amino acids), were examined. Expression of Alk5 was detected in all examined tissues, and no significant differences in the ratio of Alk5-S to Alk5-L were detected between tissues. Expression of Alk5 was also detected in various cells, with Alk5-L being especially abundant in A-6 ES cells when it was examined by RT-PCR and subsequent image analyses. No clear difference in Smad2 phosphorylation in response to treatment with TGF-beta(1) was detected between L17 cells expressing Alk5-S and those expressing Alk5-L. Consistent with these results, transcription mediated by Alk5-S in L17 cells treated with TGF-beta(1) was comparable to that mediated by Alk5-L. In addition, alternative splicing had no effect on transcriptional activation induced by GDF-8, a member of the TGF-beta family. The present results indicate ubiquitous expression of Alk5 isoforms in mouse tissues and cells, and insignificant effects of alternative splicing on signaling induced by TGF-beta(1) and GDF-8.